MEDIATION OF ACUTE BUT NOT CHRONIC REJECTION OF MHC-INCOMPATIBLE RAT KIDNEY GRAFTS BY ALLOREACTIVE CD4 T CELLS ACTIVATED BY THE DIRECT PATHWAY OF SENSITIZATION

Abstract

It has been previously postulated that there are two pathways of sensitization of MHC-incompatible kidney allografts: a direct pathway in which the host responder T cells are activated by MHC-incompatible passenger dendritic cells of the graft, and an indirect pathway, in which graft alloantigens are processed like "nominal" T cell antigens by host accessory cells, and presented as self-MHC restricted moieties. We show here that a rat AS anti-August alloreactive CD4+ T cell line, and a presumptive clone, activated through the direct pathway are capable in an adoptive transfer model of initiating rejection of normal August kidney grafts. However, neither the T cell line nor the presumptive clone initiates rejection of passenger cell-depleted August kidneys. The results support the hypothesis that direct pathway--sensitized T cells play a dominant role in early acute rejection, but not in chronic rejection.